Cystic fibrosis

Cystic Fibrosis

Done by : Layan Talib Marwa Adil Marwa Abdulsatar

supervised by : dr.RABAB

Cystic fibrosis (CF)
is a disease of exocrine gland function that involves multiple organ systems but chiefly results in chronic respiratory infections, pancreatic enzyme insufficiency, and associated complications in untreated patients. Pulmonary involvement occurs in 90% of patients surviving the neonatal period. End-stage lung disease is the principal cause of death.

Epidemiology

Cystic fibrosis is an autosomal-recessive disease. Each offspring of 2 heterozygote parents has a 25% chance of developing cystic fibrosis. Compared with males, females with cystic fibrosis have greater deterioration of pulmonary function with increasing age and younger mean age at death. Median age at diagnosis is 6-8 months

Pathophysiology

Defective CFTR results in decreased secretion of chloride and increased reabsorption of sodium and water across epithelial cells. The resultant reduced height of epithelial lining fluid and decreased hydration of mucus results in mucus that is stickier to bacteria, which promotes infection and inflammation.

Pathophysiology

Lung Mucus adheres to airway surface, leads to decreased mucus clearing Predisposition to Staph and Pseudomonas infections

Pathophysiology

Gastrointestinal Pancreas Absence of CFTR limits function of chloride-bicarbonate exchanger to secrete bicarbonate Reduced bicarbonate secretion affects the digestion so that neither endogenous nor exogenous pancreatic enzymes can work at their optimal pH reduced water content of secretions, precipitation of proteins, and plugging of ductules and acini, prevent the pancreatic enzymes from reaching the gut. Autodigestion of the pancreas occasionally leads to pancreatitis.


Intestine The pancreatic insufficiency decreases the absorption of intestinal contents. Mechanical problems associated with inflammation, scarring, and strictures may predispose the patient to sludging of intestinal contents, leading to intestinal obstruction by fecal impaction or to intussusception. Adhesions may form, leading to complete obstruction.

Pathophysiology

Gastrointestinal Biliary tree Retention of biliary secretion Focal biliary cirrhosis Bile duct proliferation Chronic cholecystitis, cholelithiasis Sweat Normal volume of sweat Inability to reabsorb NaCl from sweat as it passes through sweat duct

Symptoms

Gastrointestinal (GI) symptoms : Meconium ileus Abdominal distention Intestinal obstruction Increased frequency of stools which suggests malabsorption . Failure to thrive (despite adequate appetite) Flatulence or foul-smelling flatus, steatorrhea ( pancreatic insufficiency have fat-soluble vitamin deficiency and malabsorption of fats) Recurrent abdominal pain Jaundice GI bleeding as a result of hepatobiliary involvement.

Cough Recurrent wheezing Recurrent pneumonia Atypical asthma Dyspnea on exertion Chest pain Genitourinary symptoms : Undescended testicles or hydrocele Delayed secondary sexual development Amenorrhea
Respiratory symptoms

Genitourinary Late onset puberty Due to chronic lung disease and inadequate nutrition >95% of male patients with CF have azospermia due to obliteration of the vas deferens 20% of female patients with CF are infertile >90% of completed pregnancies produce viable infants

Physical signs

Findings related to the pulmonary system may include the following: Tachypnea Respiratory distress with retractions Wheeze or crackles Cough (dry or productive of mucoid or purulent sputum) Increased anteroposterior diameter of chest Clubbing Cyanosis Hyperresonant chest upon percussion (crackles are heard acutely in associated pneumonitis or bronchitis and chronically with bronchiectasis)


Findings related to the GI tract include the following: Abdominal distention Hepatosplenomegaly (fatty liver and portal hypertension) Rectal prolapse Dry skin (vitamin A deficiency) Cheilosis (vitamin B complex deficiency) Examination of other systems may reveal the following: Scoliosis Kyphosis Swelling of submandibular gland or parotid gland Aquagenic wrinkling of the palms (AWP)

Complications

Nasal polyps Chronic and persistent sinusitis lung Bronchiectasis Atelectasis Pneumothorax Allergic bronchopulmonary aspergillosis (ABPA) End-stage lung disease

GIT:Gastroesophageal refluxPancreatitisCystic fibrosis–related diabetes mellitusMeconium ileusDistal intestinal obstruction syndromeRectal prolapseVitamin deficiency (especially fat-soluble vitamins)

Fatty liver Focal biliary cirrhosis Portal hypertension Liver failure Cholecystitis and cholelithiasis Rickets Osteoporosis

Diagnosis

Requirements for a CF diagnosis include Signs and symptoms 2) positive genetic testing or positive sweat test findings 3) Positive family history (usually affected sibling) 4) A positive newborn screening test

Diagnostic Tests

Sweat TestMeasures chloride in person’s sweatTwo samplesEnsure false-positive does not occurNot reliable on newborns positive sweat chloride test findings (>60 mEq/L) Genetic Analysis Newborn with signs and symptoms may confirm diagnosis with blood test. Inherited disease Recommend checking family members and first cousins

Immunoreactive trypsinogen

Chest x-rays



Viscous meconium in the terminal ileum may cause intestinal obstruction.

The primary goals of CF treatment include the following:

Maintaining lung function as near to normal as possible by controlling respiratory infection and clearing airways of mucus Administering nutritional therapy (ie, enzyme supplements, multivitamin and mineral supplements) to maintain adequate growth Managing complications

Treatment

Antibiotics Nebulized, inhaled, oral, or intravenous Mucus-thinning drugs(Mucolytics) Thins secretions Easier to cough up Bronchodilators Relaxes smooth muscles in the airways


Bronchial airway drainage Postural drainage Oral enzymes and better nutrition High calorie diet Special vitamins & pancreatic enzymes Lung transplant Pain relievers Ibuprofen


The only way to cure CF would be to use gene therapy (Gene therapy is the use of normal DNA to "correct" for the damaged genes that cause disease) By inhaling a spray that delivers normal DNA to the lungs. The goal is to replace the defective CF gene in the lungs to cure CF or slow the progression of the disease. For patients with advanced stages of the disease, a lung transplant operation may be necessary.

GENE THERAPY

prognosis
Although treating the symptoms does not cure the disease, it can greatly improve the quality of life for most patients and has, over the years, increased the average life span of CF patients to 30 years. With current treatment strategies, 80% of patients should reach adulthood. Nevertheless, cystic fibrosis remains a life-limiting disease, and a cure for the disease remains elusive.

THANK YOU